Contrast media and renal function in the immature kidney.

In the immature rabbit, a real-time method for monitoring filtration fraction (FF) to demonstrate acute changes in the kidney's response to intravenous injections of contrast media was used. The renal arteriovenous difference of an agent cleared by the kidney as a pure glomerular filtrate was measured with a gamma detector, and FF was calculated by a computer and displayed on a TV monitor. The effect of FF, arterial pressure (BP), and renal blood flow (RBF) of Renografin-60 and an agent with a much lower osmolality, Iopamidol 300, was examined in anesthetized four-to five-week-old rabbits. Renografin (2 and 4 mL/kg, IV) induced dose-related decreases in FF of 40% and 73%, decreased arterial pressure by 12% and 30%, and at the 4 mL/kg dose increased RBF by 77%. Iopamidol (4 mL/kg) induced a smaller, 41% decrease in FF than the same dose of Renografin (P less than .01), a smaller, 28% increase in RBF (P less than .001), and, unlike Renografin, induced a small increase in BP. Comparison of the magnitude of the reduction of FF induced by a 2-mL/kg IV dose of Renografin in the present immature rabbits with previous results in mature rabbits shows a surprising similarity (P = .33), despite lower resting BP, RBF, and glomerular filtration rate, as well as reduced tubular function in the immature animals.

Excretion of contrast media by the immature rabbit. Comparison of Renografin and Iopamidol.

The excretion of iodinated contrast media was studied in 13 immature rabbits after the intravenous injection of 2 ml/kg (approximately 600 mg I/kg) of radio-labelled Renografin-60, a high osmolality agent (1510 mOsm/kg), or Iopamidol-300, a new agent with a much lower osmolality (616 mOsm/kg). Renografin, but not Iopamidol, induced an immediate but transient 40% fall in blood pressure, a marked diuresis that was 3.4 times greater at its maximum than for Iopamidol, and a much lower urinary iodine concentration at the time of maximum diuresis (Renografin: 90.3 +/- 9.2 microgram/ml; Iopamidol: 213 +/- 32.9 microgram/ml). No difference between the two contrast media was found for plasma iodine concentration, renal clearance from the plasma, urinary iodine excretion rate or volume of distribution. In five additional rabbit pups, formal clearance studies made using a constant IV infusion of the agents and timed collections of urine and plasma showed that Iopamidol and Renografin were cleared at the same rate by the kidneys (P greater than 0.9).

Gastrointestinal fluoroscopy: patient dose and methods for its reduction.

The aim of this study was to demonstrate a method which could be used to identify factors which contribute to the radiation exposure to patients from fluoroscopy during contrast examinations of the gastro-intestinal tract. Measurements of exposure made at the level of the X-ray tube collimator were extrapolated to obtain entrance exposure at the centre of the field and used as an index of the integral dose to the patient. Such data have heretofore been unavailable. The population studied included 65 patients ranging in age from 1 month to 21 years. In an initial study, median entrance exposure at the field centre for barium swallow examinations ranged from 0.98 to 1.7 mC/kg (3.8 to 6.6 R); barium meal: 1.9-5.7 mC/kg (7.4-22 R); barium meal with small bowel: 1.4-7.7 mC/kg (5.3-30 R); barium enema: 0.93-7.7 mC/kg (3.6-41 R). Gonadal dose, measured in males, ranged from undetectable to 0.71 mGy (71 mrad). The presence of contrast medium in the fluoroscopic field increased the exposure from a single 100 mm spot film, taken with automatic exposure control, by a factor of up to 16, and fluoroscopic exposure rate, using automatic brightness control, by a factor of 2 or more. We recommend modifications in the operation and design of fluoroscopic equipment, especially when fitted with brightness and exposure controls, for the reduction of patient exposure. Implementation of two modifications, a high/low dose switch, and a variable aperture iris diaphragm, reduced patient exposure from 1.4 to 3.4 times.

The influence of contrast medium dose on filtration fraction in the rabbit kidney.

We have examined the effect of dose on contrast medium-induced reductions in glomerular filtration in anesthetized rabbits. The fraction of renal plasma flow that is filtered, the filtration fraction, was directly measured by the renal arteriovenous difference method using technetium-99m (99mTc) (Sn) DTPA as the tracer, arterial and renal venous extracorporeal shunts, a gamma camera and a computer. Filtration fraction (FF) was measured each 30 seconds before and after contrast medium (sodium/methylglucamine diatrizoate) was injected in 15 seconds at a dose of 0.5, 1.0 or 2.0 ml/kg, IV. In six animals that had a control FF of 0.19 +/- 0.01 there was a dose-related decrease in FF. The largest dose reduced FF by 53.3%. In three other animals that had a low control FF (0.07 +/- 0.01), the largest dose induced an even greater 71.0% decrease in FF. These data suggest that attempts at increasing contrast excretion by injecting larger doses will be offset, at least in part, by larger reductions in glomerular filtration, and that this effect may be greater when glomerular function is impaired.

The effect of contrast media on immature renal function. Comparison of agents with high and low osmolality.

Contrast media having high osmolality (methylglucamine diatrizoate; 1,510 mOsm/kg) and low osmolality (triiodoisophthaldiamide, 616 mOsm/kg) were compared in 15 functionally immature rabbits 2-3 weeks of age. Renal function was assessed with a gamma camera and whole-body counter, using excretion of technetium-99m-tin-DTPA as an index of glomerular filtration rate. Both DTPA and the contrast agent (2 ml/kg) were injected as a single intravenous bolus in 15 seconds. After 40 minutes, per cent DTPA excreted was 33.0 +/- 2.3 for triiodoisophthaldiamide and 28.2 +/- 1.5 (p less than 0.01) for methylglucamine diatrizoate. Excretion of DTPA was reduced with the latter (p less than 0.005) but not the former agent (p greater than 0.6). Thus contrast materials with high osmolality depress renal function in immature rabbits, suggesting that agents with low osmolality are preferable for use in newborns.

Reactions to intravenous contrast media. Part II: Acute renal response in euvolemic and dehydrated dogs.

Growing concern about acute renal failure as the result of contrast agents prompted an investigation into the renal effects of intravenous contrast materials in euvolemic and dehydrated dogs. Bolus injection of hypertonic agents induced marked reductions in filtration fraction and glomerular filtration rate in both groups of animals; however, these changes were transient, returning to near-base-line values within 30 minutes after injection. The most striking differences between euvolemic and dehydrated animals appeared to be related to prerenal factors such as hypovolemia and contrast-induced hypotension.

Mechanism of the renal response to contrast medium in dogs. Decrease in renal function due to hypertonicity.

Radiographic contrast media (CM) (meglumine/sodium diatrizoate-76%; 1650 mOsm/kg) and other hypertonic solutions induce renal vasoconstriction by an unknown mechanism. In anesthetized dogs, renal blood flow (RBF) was measured with an electromagnetic flowmeter and filtration fraction (FF) and glomerular filtration rate (GFR) by the renal extraction of technetium-99m tin chelate. Ureteral pressure (UP) and wedged renal venous pressure (VP) were measured as indices of intrarenal pressure. Measurements of renal length (L), along with pressures, made it possible to examine the compliance of the system. A 4-cc intrarenal bolus of CM caused a 59% reduction in GFR (control: 0.63 +/- 0.04 to 0.26 +/- 0.04 ml/min X g, mean +/- SEM), in association with a 23% reduction in RBF (control: 3.10 +/- 0.11 to 2.39 +/- 0.26 ml/min X g) and a 44% decrease in FF (control: 0.32 +/- 0.01 to 0.18 +/- 0.03). These responses were compared with a 3-microgram intrarenal bolus of norepinephrine (NOREPI) which resulted in a 79.0 +/- 7.5% reduction in RBF, 68.3 +/- 7.3% reduction in GFR and 42.6 +/- 15.6% increase in FF. The NOREPI-induced vasoconstriction caused transient decreases in renal L, UP, and VP, whereas the CM-induced decrease in renal blood flow was associated with increases in these parameters. In studies employing ureteral occlusion to elevate intrarenal pressure, the magnitude (area, cm2) of the CM-induced decrease in renal perfusion was accentuated with increased UP (r = 0.79, n = 24, P less than 0.001). The CM-induced increase in renal L, UP, and VP must reflect osmotic forces and an increase in intrarenal pressure. The decreases in FF and GFR probably reflect Starling forces in the glomerular capillaries, with osmotic transients dominating. The results suggest a mechanical mechanism for the CM-induced decrease in RBF.

Loss of the glomerular contractile response to angiotensin in rats following myohemoglobinuric acute renal failure.

To examine the state of the glomerulus in rats protected from acute renal failure (ARF) by prior insult, we measured the contractile responses of isolated glomeruli to angiotensin II (AII) and dibutyryl cyclic AMP (DBcAMP). In healthy rats, both agents induced a dose-related fall in glomerular diameter (P less than 0.001). Saralasin, the angiotensin antagonist, blocked the glomerular response to AII totally and to DBcAMP partially. Two weeks following ARF induced with 50% glycerol (10 ml/kg, im), azotemia had reversed and the nephrotoxic effect of mercuric chloride (4.7 mg/kg, sc) was blunted, as anticipated. AII did not reduce glomerular size, but the response to DBcAMP was sustained at this time. To determine the specificity of the loss of the glomerular response to AII, we also assessed the effects of an AII infusion (1 microgram/kg/min) on blood pressure and renal blood flow. There was a substantial rise in blood pressure (control, 104 +/- 11.8 mm Hg; AI, 131.0 +/- 5.3 mm HG; P less than 0.001) and fall in renal blood flow (control, 2.45 ml/g per min; AII, 0.81 +/- 0.10 ml/g per min; P less than 0.025). Vascular responsiveness to AII was preserved at a time when glomeruli were totally unresponsive and rats were resistant to ARF. The loss of glomerular contractility may, in part, account for the protection from ARF seen in this model: if so, glomerular abnormalities may play a pathogenetic role.

The influence of increased renal mass on cardiovascular function in immature dogs.

Pediatric renal allograft recipients receive a relatively greater increase in renal mass than do adult recipients because the donors are usually adults. They also have a higher frequency of posttransplant hypertension and cardiovascular problems. Avoiding other variables common to both pediatric and adult patients including pre-existing hypertension and renal disease and the use of corticosteroids, renal mass was increased by up to 50% in immature dogs by implanting large kidneys from adult dogs. Cardiovascular and renal function were studied before and after transplantation. Blood pressure was decreased in anesthetized mongrel pups at 2 hr and 3 days after surgery by 22 and 6 mm Hg, respectively; pressure was similarly reduced in conscious, chronically catheterized DLA-matched beagle pups maintained for 14 days, from 96.1 +/- 3.0 to 76.8 +/- 6.7 mm Hg (P less than 0.001). Glomerular filtration rate was decreased at 2 hr and 3 days, but was normal at 14 days. Cardiac output was reduced in four of five recipients at 2 hr but was unchanged at 3 days. Plasma volume was increased at 3 days in the mongrel dogs but was normal in the beagles both at 2 and 14 days. We conclude that an increase in renal mass of up to 50% by itself does not cause hypertension in the dog and that other factors may be implicated in pediatric allograft recipients.

Angiotensin receptors in glomeruli differ from those in renal arterioles.

Angiotensin receptors in afferent and efferent arterioles and in the glomerulus are strategically located to influence renal perfusion and glomerular function. With the size of isolated glomeruli as the index, we have demonstrated identical dose-response relationships for graded concentrations (10(-13) to 10(-3) g/liter) of angiotensin II (AII) and angiotensin III (AIII). An octapeptide analogue (saralasin 10(-6) to 10(-2) g/liter) was equally effective at blocking glomerular responses to both AII and AIII, but two heptapeptide analogues (des-asp, 8-ile AII and des-asp, 8-gly AII; 10(-6) to 10(-2) g/liter) failed to block responses to either agonist. The relative influence of octapeptide and heptapeptide analogues on GFR was examined in anesthetized dogs with partial occlusion of the thoracic inferior vena cava. In 18 dogs, caval occlusion reduced renal blood flow (35%), GFR (29%), and arterial pressure (13%). Saralasin (300 to 3000 ng/kg/min, i.v.) and des-asp, 8-ile AII (100 to 3000 ng/kg/min, i.v.) increased renal blood flow by 0.41 +/- 0.11 and 0.62 +/- 0.11 ml/g/min, respectively, but only the octapeptide induced a concomitant increase in GFR (octapeptide: delta GFR = 0.11 +/- 0.03 ml/g/min; heptapeptide: delta GFR = -0.08 +/- 0.07 ml/g/min; P less than 0.025). As octapeptide and heptapeptide analogues were equally effective on renal blood flow in this and in previous studies, but only the octapeptide was effective in isolated glomeruli and in increasing GFR in the intact animal, we conclude that renal vascular and glomerular receptors differ. Furthermore, the glomerular receptor may be the more important in modulating the glomerular functional response to angiotensin.

Inguinal herniation of the ureter.

A case of ureteral herniation into the inguinal canal is reported in a 6 week old boy with a solitary functioning kidney.

Angiotensin antagonists with increased specificity for the renal vasculature.

This study was designed to ascertain whether renal vascular angiotensin receptors differ from other systemic angiotensin receptors and whether, on that basis, antagonists with greater specificity for the renal vasculature can be defined. Femoral and renal blood flow and their responses to angiotensin II (AII) and its heptapeptide analogue, 1-des Asp AII (AIII), were measured with an electromagnetic flowmeter in 26 dogs. For the kidney, the threshold doses of AII and AIII were identical (2.5+/-0.27 vs. 2.3+/-0.35 pmol/100 ml renal blood flow, with similar dose-response curves. In contrast, AII had a greater pressor effect (P less than 0.001) and produced more femoral vasoconstriction (P less than 0.001) than AIII. All four antagonists studied (1-Sar, 8-Ala AII [P113]; 8-Ala AII; 1-des Asp, 8-Ala AII; 1-des Asp, 8-Ile AII) induced parallel shifts in the renal blood flow response to AII and AIII. P113 induced greater blockade than 8-Ala AII (P less than 0.001) which, in turn, was more effective than 1-des Asp, 8-Ala AII (P less than 0.001). 1-des Asp, 8-Ile AII was as effective as P113. Each analogue induced an identical inhibition of the renal vascular response to AII and AIII. In addition, AII and AIII induced cross-tachyphylaxis. All lines of evidence suggested that AII and AIII act on a single receptor in the kidney, which differs at least functionally from other systemic vascular receptors. The possibility that heptapeptide analogues represent angiotensin antagonists with greater specificity for the renal vasculature was pursued in a model in which the renin-angiotensin system is activated. Acute, partial thoracic inferior vena caval occlusion was induced in an additional 16 dogs. P113 induced progressive, dose-related hypotension and a limited increase in renal blood flow in this model. The 1-des Asp, 8-Ile AII analogue, conversely, induced a consistent, larger, dose-related renal blood flow increase, with significantly less hypotension over a wide dose range. We conclude that the renal vascular receptor differs sufficiently from systemic angiotensin receptors that heptapeptide analogues of AII will be useful in exploring angiotensin's role in states characterized by disordered renal perfusion and function.